Transient outward K+ current (ITO) reduction prolongs action potentials and promotes afterdepolarisations : a dynamic-clamp study in human and rabbit cardiac atrial myocytes

Workman, A.J. and Marshall, G.E. and Rankin, A.C. and Smith, G.L. and Dempster, J. (2012) Transient outward K+ current (ITO) reduction prolongs action potentials and promotes afterdepolarisations : a dynamic-clamp study in human and rabbit cardiac atrial myocytes. Journal of Physiology, 590 (17). 4289–4305. (https://doi.org/10.1113/jphysiol.2012.235986)

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Abstract

Background & aim. Human atrial transient outward K+ current (ITO) is decreased in a variety of cardiac pathologies, but how ITO reduction alters action potentials (AP) and arrhythmia mechanisms is poorly understood, owing to non-selectivity of ITO blockers. Aim: to investigate effects of selective ITO changes on AP shape and duration (APD), and on afterdepolarisations or abnormal automaticity with beta-adrenergic-stimulation, using the dynamic-clamp technique in atrial cells. Methods & Results. Human and rabbit atrial cells were isolated by enzymatic dissociation, and electrical activity recorded by whole-cell-patch clamp (35-37oC). Dynamic-clamp-simulated ITO reduction or block slowed AP phase 1 and elevated the plateau, significantly prolonging APD, in both species. In human atrial cells, ITO block (100% ITO subtraction) increased APD50 by 31%, APD90 by 17%, and APD-61mV (reflecting cellular effective refractory period) by 22% (P

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